The imidazole ring of histidine exists in two tautomeric forms in neutral-to-basic aqueous solution, and the tautomerism of the histidine residue sometimes plays a key role in catalytic reactions of enzymes. We have investigated the molecular vibrations of two tautomers of 4-methylimidazole (4-Melm), a model compound for the histidine side chain, by Raman spectroscopy and ab initio calculations based on the density functional theory (DFT) approach. Examination of the temperature dependence of Raman intensity revealed nine pairs of bands characteristic of the N1-protonated and the N3-protonated tautomers of 4-Melm at 1576/1596, 1452/1427, 1304/1344, 1265/1259, 1229/1234, 1165/1149, 1088/1104, 996/1014, and 942/934 cm(-1). Five to six pairs of tautomerism-sensitive Raman bands were also identified for each of the C2-, N-, and C2,N-deuterated analogues of 4-Melm. The observed Raman wavenumbers were used to determine nine scaling factors for the in-plane force constants derived from DFT calculations using the 6-311+G(2d, p) basis set. The force field finally obtained reproduces the experimental vibrational wavenumbers of four additional isotopomers (C5-, C5,N-, C2,C5-, and C2,C5,N-deuterated 4-Melm) as well. The vibrational modes calculated for 4-Melm are useful in understanding the origins of the previously proposed tautomer marker bands of histidine at 1568/1585, 1282/1260, 1090/1105, and 983/1004 cm(-1). A pair of Raman bands at 1320/1354 cm(-1) is suggested to be a new tautomer marker of histidine.